酪氨酸羟化酶与钩藤碱抑制甲基苯丙胺依赖小鼠条件性位置偏爱的关系研究  

Effect of rhynchophylline on expression of TH in methamphetamine-induced CPP mice

作　　者：朱晨 刘伟 李璟 李婵 房淼 陈志杰 周玉婷 罗超华 莫志贤 ZHU Chen;LIU Wei;LI Jing;LI Chan;FANG Miao;CHEN Zhi-jie;ZHOU Yu-ting;LUO Chao-hua;MO Zhi-xian(Dept of Traditional Chinese Medicine Pharmacology,School of Traditional Chinese Medicine,Guangzhou 510515,China;Central Lab,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学中医药学院中药药理学教研室,广东广州510515 [2]南方医科大学中心实验室,广东广州510515

出　　处：《中国药理学通报》2018年第9期1226-1230,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81673628;81573706)

摘　　要：目的研究酪氨酸羟化酶(tyrosine hydroxylase,TH)与钩藤碱抑制甲基苯丙胺依赖小鼠条件性位置偏爱(condition place preference,CPP)作用的关系。方法实验分为5组:空白对照组、模型组、钩藤碱低剂量组(40 mg·kg^(-1))、钩藤碱高剂量组(80 mg·kg^(-1))、氯胺酮组(15 mg·kg^(-1))。腹腔注射甲基苯丙胺后,进行小鼠条件性位置偏爱训练,建立小鼠甲基苯丙胺CPP依赖模型,分析各组小鼠在CPP箱中的活动,以及各组小鼠脑内TH的表达情况。结果给予甲基苯丙胺4 mg·kg^(-1)后,甲基苯丙胺依赖小鼠CPP模型成功建立。与空白组相比,模型组小鼠在伴药箱中的时间明显增加;与模型组相比,钩藤碱组小鼠在伴药箱中的时间明显减少。与空白组相比,模型组小鼠脑内TH阳性细胞数明显增加;在给予钩藤碱干预后,小鼠脑内TH阳性细胞数明显减少。与空白组比较,模型组小鼠脑内TH蛋白表达明显增强,给予钩藤碱干预后,TH蛋白表达减弱。结论钩藤碱在一定程度上可以抑制甲基苯丙胺诱导的小鼠CPP效应,其作用机制可能与TH的表达有关。To explore the effect of rhynchophylline on the expression of tyrosine hydroxylase(TH)in hippocampus of methamphetamine-induced condition place preference(CPP)mice.Methods Metham-phetamine was injected intraperitoneally to mice,and the expression of TH was observed by immunohistochemistry and Western blot.Results The CPP mouse model was established successfully by methamphetamine(4 mg·kg-1).Ketamine(15 mg·kg-1),rhynchophylline low dosage group(40 mg·kg-1)and rhynchophylline high dosage group(80 mg·kg-1)could remove the effect of methamphetamine on CPP mice.The result of immunohistochemistry showed that methamphetamine(4 mg·kg-1)could increase the number of TH positive cells in hippocampus while ketamine(4 mg·kg-1),rhynchophylline(40,80 mg·kg-1)group could attenuate the change.Western blotting indicated the expression of TH of model group increased significantly,whereas ketamine(15 mg·kg-1),rhynchophylline(40,80 mg·kg-1)group presented less expression.Conclusions The CPP induced by methamphetamine in mice may be inhibited to some extent by rhynchophylline,and its mechanism may be associated with the expression of TH.

关 键 词：钩藤碱 甲基苯丙胺 条件性位置偏爱 药物依赖 酪氨酸羟化酶 氯胺酮 

分 类 号：R-332[医药卫生] R284.1